The objective of the Cerebral Vascular Disease Research Center at the University of Miami is to carry out an integrated, multi-disciplinary program of experimental research into the mechanisms and therapies of ischemic brain injury. The overall goal of our research program is to identify and characterize those factors responsible for engendering ischemic injury that may be amenable to therapeutic or prophylactic intervention. The Program Project consists of three investigative proposals supported by General-Scientific and Image- Analysis/Computing Core facilities. Project areas include 1) focal cerebral ischemia: a study of the mechanisms of neuroprotection underlying human serum albumin therapy, and of exacerbation of injury due to hyperthermia (fever); 2) mitochondria and cerebral anoxia/ischemia: basic mechanistic studies of protection and dysfunction; and 3) the metabolic and structural consequences of evolving mitochondrial and ionic dysfunction in focal ischemia. The projects are closely integrated with one another, both conceptually and methodologically, and are strongly supported by close collaborative interactions among the investigators and research personnel. The core facilities contribute substantively to the implementation of each project and unify the overall program by common methodological approaches. The General Scientific Core compromises animal physiology; methods of focal and global cerebral ischemia; neurobehavioral strategies; morphological methods including quantitative light microscopy and stereology; immunohistochemistry, confocal microscopy; autoradiographic strategies for local cerebral blood flow and glucose utilization; enzymatic tissue sampling and metabolic analyses; and molecular biological methods, including in situ hybridization, Northern and Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR). The Image-Analysis and Computing Core has pioneered in the development of three-dimensional autoradiographic image-averaging and is a central resource supporting image-analysis of autoradiographic, molecular biological, and histopathological data; as well as acquisition, statistical analysis and archiving of laboratory data, instrumentation control, and data base management.